The objective of this proposal is to further our understanding of the mechanisms by which chondrocytes respond to dynamic mechanical load. Tissue transglutaminase (tTG) stabilizes extracellular matrix of many tissues, including cartilage, via the cross-linking of proteins such as fibronectin and collagen and may be important for the strengthening or remodeling of cartilage matrix in response to dynamic load. Furthermore, disruption of normal tTG functioning may contribute to the development or progression of osteoarthritis. The aims of this proposal are: l) to examine by immunocytochemistry and in situ hybridization the expression and localization of tTG in chondron pellet cultures before and after cyclic compressive loading; 2) to measure the cross-linking activity of tTG in response to cyclic compressive loading in chondron pellet cultures by examining the incorporation of exogenous tTG substrates; 3) to identify immunologically the endogenous matrix proteins which are cross-linked by tTG in loaded chondron pellets, and determine the pattern of cross-linking induced by loads of different strengths. These studies will provide a clearer understanding of the role of tTG in articular cartilage.